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Function

PDE5 is an phosphodiesterase : this enzyme catalyzes the hydrolysis of cGMP into 5'GMP. CGMP is an usual second messager in cell transduction. PDE5 regulates its concentration by hydrolysis. Human PDE5 is a PDE of class I. PDE5 function affects the smooth muscle, blood vessels or penis, uterus and intestines.

Structural highlights

PDE5 is a dimeric protein of about 270 amino acids long. The C terminal has the catalytic domain and two Zn2+ binding site and N temrinal is the regulatory domain which includes two the GAF domain a and b. There are thus plural allosteric binding site for cGMP in the Cterminal and the N terminal. cGAMP binds on Gap an allosteric site and promotes the phosphorylation of SER 92 of PKG. This phosphorylation increases the affinity between cGMP and PDE5. Another cGMP can bind to the Gap b which allows the activation of the catalytic site of PDE5. The activated catalytic site is now able to break the phosphodiesteric bond of cGMP  :http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518390/)

Catalytic activity

Some residues could be affected by post traductional modifications : - phosphorylation : S60, S86, S92, S102, S104, S108, T111, T127, T137, S869 - acylation : K364 - ubiquitinylation : K714

The ubiquitinylation of (in fushia) and the phosphorylation of are involved in the binding of cGMP to PDE5 catalytic domain.

Inhibitors and medical application

If an inhibitor binds instead of cGMP, cGMP concentration increases and the stimulus continues. PDE5 inhibition is particulary used for erectile disfunction. Sildenafil or VIagra is an inhibitor of PDE5.

GLN 775 and GLN 817 of PDE5 interacts through hydrogen bonds with

Allosteric activation

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